To develop new treatments for cancer, scientists are focused on finding the malfunctioning machinery within cancer cells that can be targeted using small molecule pharmaceuticals. Now, University of Michigan researchers have identified one of these targets: a zinc and calcium ion permeable channel within a cell’s lysosome, the organelle responsible for recycling cellular waste, nutrient sensing and cell metabolism.
The researchers discovered that this channel is upregulated—meaning both its protein expression and channel activity were substantially increased—in metastatic melanoma cells compared with healthy melanocytes. They found that targeting this channel protein with small pharmaceutical compounds triggers the rapid and selective death of cancer cells while completely sparing normal cells. Their research is published in the journal Cell Reports.
“Many traditional cancer therapies target a well-known cell death pathway called apoptosis to trigger cancer cell death. However, many aggressive cancer cells harbor numerous mutations of genes that help them escape these treatments. We saw an urgent need to develop new therapeutic strategies that target nonapoptotic cell death pathways to eradicate cancer cells,” said Wanlu Du, an assistant research scientist in the U-M Department of Molecular, Cellular, and Developmental Biology.
In metastatic cancers, lysosomes turn hypertrophic, which means they actively contribute to tumor progression by increasing their ability to provide nutrients to the rapidly dividing cells and secreting enzymes to digest extracellular matrix—the material that provides the physical scaffolding for cells to help cancer cell invasion. But designing cancer therapies that target lysosomes may also harm normal cells and tissues by compromising lysosomes’ ability to provide nutrients for healthy cells.